Field of the Invention
The present invention relates to a use of gallic acid (GA) and its pharmaceutically acceptable salt and ester, especially in healthcare. In particular, the present invention relates to a method for alleviating at least one of the disturbance of bile acid metabolism, disturbance of amino acid metabolism and disturbance of gut microbiota metabolism by using a gallic acid and/or a pharmaceutically acceptable salt and/or ester of gallic acid.
Description of the Related Art
Gallic acid, also known as wubeizi acid or bei acid, is a natural polyphenolic compound that exists in various parts of natural plants. For example, it is found in the root and the stem of Rheum palmatum L. in Polygonaceae, the leaves of Eucalyptus robusta Smith in Myrtaceae, the fruit of Cornus officinalis Sieb. et Zucc in Cornaceae, the flower of Lythrum salicaria Linn. in Lythraceae, the leaves of Coriaria intermedia Matsum. in Coriariaceae, the pericap of Punica granatum L. in Punicaceae, etc. Gallic acid has low toxicity and good safety and its No Observed Adverse Effect Level (NOAEL) in a mouse is greater than 5000 mg/kg. Also, gallic acid shows no negative response in rat toxicological research. Therefore, gallic acid has a high potential for development. It has been known that Gallic acid has various biological activities, such as anti-oxidation, anti-inflammatory, anti-tumor, obesity control, liver protection, etc., while the mechanisms of such activities are still unclear.
The diet, trophic structure and lifestyle of people in modern society are undergoing tremendous changes, and the morbidity of hypertension, hyperlipidemia, atherosclerosis, tumor and other metabolic disorders have also increased. Researches have found that in the proceeding of these diseases, the biochemistry metabolism in organism would change, such as the occurrence of the disturbance of amino acid metabolism. The previous studies have found that in the proceeding of the above diseases, the occurrence of the disturbance of amino acid metabolism is correlated to and has causal relationship with the diseases. That is, one single metabolic disease could develop into a variety of coexisting diseases. Therefore, it will be a significant benefit for the above diseases if the disturbance of amino acid metabolism can be alleviated.
The disturbance of bile acid metabolism is also a cause for a lot of diseases. Bile acid, a general designation of 24-carbons cholanic hydroxyl derivatives, is a major solid component of bile, and is an endogenous organic anion. There are fifteen (15) kinds of bile acid in human bile, comprising primarily cholic acid, chenodeoxycholic acid, deoxycholic acid, small amounts of lithocholic acid and trace amounts of ursodeoxycholic acid. Bile acid is the major permeating active material with a function of cholagogue, and can increase the secretion and elimination of bile. It plays a role of anti-microbes in the bile duct and intestine and in preventing the bacterial overgrowth in bile duct and intestine and the shift of enteric microflora. If the disturbance of bile acid metabolism occurs in a human body, it will result in the appearance of associated diseases such as cholestasis liver diseases, cholestasis, bile duct infection, bile duck stones, congenital bile duct diseases, etc.
In addition, in a normal human body, there is a certain balance between the enteric microflora and the host in the gastrointestinal tract. The enteric microflora in human gastrointestinal tract serve various important functions such as promoting digestion, increasing nutrition, regulating immunity, inhibiting the proliferation of harmful microbe, anti-tumor, anti-aging, etc. The related studies have indicated that if the relationship between the enteric microflora and the host is imbalance, it will result in associated diseases such as aging, inflammatory enteritis, depression disorder, anxiety disorder, immune disorder, allergy, etc (see Ann Hepatol. 2012 July-August; 11(4):440-9., Sci Transl Med. 2012 Jun. 6; 4(137):137, Nat Rev Immunol. 2009 May; 9(5):313-23. Cell. 2012 Mar. 16; 148(6):1258-70, which is entirely incorporated hereinto by reference). Therefore, the intestine microbe is becoming an important target of a new medicament in recent years. If the disturbance of the enteric microflora can be alleviated, the progression of the above diseases could be ameliorated.
For the above metabolic mechanisms, the inventors of the present invention found that gallic acid has the effects of alleviating the disturbance of metabolism, such as alleviating the disturbance of bile acid metabolism, the disturbance of amino acid metabolism and/or the disturbance of gut microbiota metabolism in the diseased body. Therefore, in addition to helping with metabolism, gallic acid can be used for daily health care.